Zhuo Renxi

Template-module assembly to prepare low-molecular-weight gene transport system with enhanced transmembrane capability

Based on specific host-guest interactions between amine-modified β-cyclodextrin (CD-TAEA) and functional adamantane (AD) derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assemblies for gene transport. This strategy offers great flexibility in terms of the introduction of mono- or multi-functionality by the inclusion of one or more adamantane-based modules with the desired functionalities. As proof of concept, phenylboronic acid (PB) containing adamantane (PB-AD) was used as a model module in the hope of offering enhanced cytosolic delivery in consideration of the special affinity of PB groups with cell membranes. The physicochemical properties of the complexes formed with plasmid DNA, such as particle size, zeta potential and morphology were investigated. Confocal laser scanning microscopy and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the considerably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CD-TAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CD-TAEA displayed much lower cytotoxicity than PEI25K in both 293T and HeLa cell lines. The encouraging results suggest that CD-TAEA can be developed as a powerful template capable of readily accommodating various AD-based modules giving versatile functionalities for improved transfection.

A Three-drug co-Delivery System Based on Reduction-sensitive Pol-ymeric Prodrug to Effectively Reverse Multi-drug Resistance

In the present study, we prepared a multi-drug delivery system based on reduction-sensitive paclitaxel (PTX) polymeric prodrug(PEG-b-PMPMC-g-PTX, PMP) polymersomes to co-deliver PTX, doxorubicin hydrochloride(DOX·HCl) and the P-glycoprotein(P-gp) inhibitor Tariquidar(TQR) to effectively reverse drug resistance by inhibiting the expression of P-gp and improving the accumulation of the encapsulated anticancer drugs. The PTX was linked to the backbone by reduction-sensitive disulphide, making the polymersomes prone to collapse in the reductive environment and to release the drugs. Transmission electron microscope(TEM) was used to confirm the morphology of polymeric assemblies. Moreover, the rupture process of polymersomes was verified by dynamic light scattering (DLS). The results of confocal laser scanning microscopy(CLSM) and flow cytometry indicate that the PMP/DOX·HCl/TQR three-drug-loaded polymersomes show the strongest fluorescence intensity for DOX·HCl compared with PMP/DOX·HCl polymersomes and free DOX·HCl in drug-resistant MCF-7/ADR cells. More importantly, the PMP/DOX·HCl/TQR multi-drug co-delivery system shows a greater growth-inhibitory effect on tumour cells than the other two samples, including PMP/DOX·HCl nanoparticles without the TQR component and free DOX·HCl, when co-incubated with either nonresistant HeLa cells or drug-resistant MCF-7/ADR cells. This growth-inhibitory effect was especially evident in drug-resistant cells. These results imply that the co-delivery of PTX, DOX·HCl and TQR based on reduction-sensitive polymeric prodrug may be promising for overcoming multi-drug resistance in tumour treatments.

Study on synthesis and herbicidal activity of heterocyclic compounds containing P-P bond

N,N′-diphenylurea reacted with phosphorus trichloride and phenyl dichlorophosphane giving the heterocyclic compounds 1 and 2 with a direct phosphorus-phosphorus bond (P-P bond), respectively. The new compounds were characterized by elementary analysis, NMR and IR spectra. The results of preliminary bioassay showed that these heterocycles possess selective herbicidal activity at 1.5 kg/hm2.

The design and application of functionalized mesoporous silica nanocarrier

With the rapid development of nanotechnology, nanomaterials with unique physical and chemical characteristics, have offered tremendous potential for biomedical application. Among them, mesoporous silica nanoparticles (MSNs), a class of well-established nanoplatforms with different structures and compositions, have been widely used to develop drug delivery systems owing to their unique physical-chemical properties, such as tunable particle/pore size, high surface area and pore volume, easy surface modification, remarkable stability and biocompatibility, and high drug loading efficiency. Moreover, MSN-based nanocarriers with “zero premature release” property have proven to be excellent devices for drug delivery. A variety of fluorescent dyes and pharmaceutical drugs were encapsulated in MSNs for controlled release. In addition, numerous efforts have been made to develop smart nanovalves on the surface of MSN to provide on-command release of drug in response to different stimuli, including light, enzymes, pH, redox, temperature, and competitive molecules. Furthermore, the outer surface of MSN can be modified with various functional groups, that play critical roles (stealth or targeting) in overcoming the multistage barriers found in the drug delivery process. Fabrication of MSN-based, multifunctional, stimuli-responsive drug delivery systems can effectively encapsulate anticancer drugs and can maintain “zero premature release” before reaching the diseased site. Once they arrive at the tumor site with the aid of targeting groups, the nanodevice can be activated by a specific stimulus to release the drug. The delivery of anticancer drugs to a specific target site can alleviate toxic side effects and improve the therapeutic index of drugs; thus, achieving significantly enhanced anticancer efficiency. Herein, we reviewed various strategies for the design of stimuli-responsive, MSN-based drug delivery systems, and multifunctional MSN for targeted cancer therapy.

Molecular self-assembly of peptide

Arising from the abundant protein self-assemblies existing in nature, recently, the self-assembly of peptides has been a research focus. Through rational designing the molecular structures of peptides and altering the external environment, peptides can spontaneously or induced self-assemble into specific-shape aggregates via noncovalent forces, such as hydrogen bonding, hydrophobic and π-stacking interactions etc. Due to well biocompatibility and controlled degradation, functional materials constructed from the self-assembly of peptides present a great potential in many biomedical fields. This review explores the research progress of the self-assembly of peptides in the past two decades. The structure motifs used in the self-assembly of peptide, self-assembly mechanisms, morphologies as well as the biomedical applications of the self-assembled peptides are also reviewed in detail.

Ultrasonic Degradation of Biosynthetic Poly (3-Hydroxybutyrate.co.Hydroxyvalerate)

In this article, ultrasonic degradation of copolymers— poly (3-hydroxybutyrate-co-hydroxyvalerate) (PH-BV) was first reported. Effect of reaction conditions on the degradation rate was investigated. By ultrasonic irradiation we find that copolymers with narrower molecular weight distributions and higher purity can be obtained in a short time and chain cleavage takes place at HV block.

Synthesis and application of pH sensitive immobilized enzyme carriers with reversible solubility-precipitation property

pH sensit ive te rpolymers with reversible solubil i ty-precipi tat ion proper ty when the pH values of the solution were changed were synthesized by terpolymerizat ion of acrylic acid, methyl methacrylate and maleic anhydride. The chemical s t ruc ture of these te rpolymers obtained was characterized by IR spec t rum. The critical pH values of solubi l i ty-precipi tat ion of these te rpolymers were investigated. Immobilization of papain on these polymers were also carried out.

Immunostimulatory properties of a novel polyphosphoramidate based on stearyl tyrosine

The immunostimulatory property of a synthetic polyphosphoramidate based on stearyl tyrosine (PPST) is described. The immunostimulatory activity of this negatively charged polymer was investigatedin vitro through examining the effect on the mitogen-induced lymphocytes proliferation by a tetrazolium-based colormetric assay and also through studying the primary plaque-forming cells (IgM PFC) responses of Balb/c mice after the intraperitoneal (i.p.) injection of the polymer with sheep red blood cells (SRBC). PPST exhibits specific and high immunostimulatory activityin vitro by the stimulation on lipopolysaccharide(LPS)-induced murine B-cells proliferation, which is probably due to the interaction between the polymer with LPS-responding B lymphocytes. This polymer also makes a significant increase of single antibody producing cells. The result shows that the stimulation rate to IgM PFC response of Balb/c mice achieved 77.9% (p<0.01) when 160 mg/kg of PPST was injected 4 h before with SRBC.

Synthesis of poly(glycolide-CO-2-hydro-2-oxo-1,3,2-dioxaphosphorinane)

A novel polyester containing glycolic acid (GA) and 2-hydro-2-oxo-1,3,2-dioxaphosphorinane (TMP) was prepared by ring-opening polymerization. The composition and the structure of the titled polymer were investigated by1H NMR,13C NMR, FT-IR, EA, and VPO. The influence of time on total conversion and molecular weight was also studied.

Studies on the melt copolymerization of phosphorus-containing diacid and bis(p-carboxyphenoxy) propand for DDS

EIn: Wuhan Daxue Xuebao (Ziran Kexue Ban), 1997,43(4) : 468~ 470] STUDIES ON THE MELT COPOLYMERIZATION OF PHOSPHORUS-CONTAINING DIACID AND BIS(p-CARBOXYPHENOXY) PROPAND FOR DDS Fu Jie,Zhuo Renxi,Fan Changlie (Department of Chemistry,Wuhan University,Wuhan 430072 ,China) Phosphorus containing copolyanhydrides DECP-CPP and DCPP-CPP were synthesized by melt copolymerization of bis (p -ca rboxy phenyloxy e t hy l ) , ethyl phosphate ( D C P E ) , bis (p -ca rboxypheny loxy e t h y l ) , phenyi phosphate ( D C P P ) and bis ( p c a r b o x y p h e n o x y ) p r o p a n e acid ( C P P ) . The copolyanhydrides were characterized by ~H N M R , IR spect rometry . In Vitro degradation of copolyanhydrides in phosphate buffer solution at 37 C were determined. Drug release profile of Rifampicinum ( R F P ) were also studied.